Obesity and early life

One hundred years ago, reports in the national press claimed that two-thirds of the young men who volunteered to fight in the South African war had been rejected because of poor physique. An interdepartmental committee was set up to report on the physical deterioration of the British nation (1). It drew a shocking picture of the nation’s children – malnourished, thin, stunted. The report led to a series of public health reforms, including the founding of school health services and the Midwives Act. France and Germany had already implemented such programmes. When in 1904 the Lancet sent representatives to Paris, they found that free meals of soup, meat and vegetables were being provided for each school child. We are now in a new cycle of physical deterioration of the British nation. The focus of concern is that the rising rates of childhood obesity will fuel the epidemic of chronic diseases, including coronary heart disease, raised blood pressure and adult-onset ‘type 2’ diabetes. One view is that childhood obesity and adult disease are being initiated by excess nutrition in utero or during infancy. People who become obese tend to have high birthweight and above-average weight through infancy 2-4). The path of growth that leads to obesity-related disease begins, however, with low birthweight and small body size during infancy 5-14). Through the discovery of a large collection of child growth records in Helsinki, Finland, it has recently become possible to link serial measurement of children’s growth to their experience of chronic disease in later life (9). Figure 1 is based on 8760 people who were born in Helsinki during 1934–1944. Each person had on average 18 measurements of height and weight between birth and 11 years of age. Figure 1a shows the mean height, weight and body mass index (BMI, that is weight/height2) of the boys at each month from birth to 2 years of age and at each year from 2 to 11 years (9). Body size is expressed as z-scores (standard deviation scores) and the average z-scores for all the boys are set at zero. A boy maintaining a steady position as tall or short, fat or thin, in relation to other boys would follow a horizontal path on the figure. The average body size of the boys who later developed coronary heart disease was below the average at birth. It fell further so that they were thin and short at 1 and 2 years of age. After 2 years, their z-scores for BMI began to increase and continued to do so. Mean z-scores for height, weight and BMI in the first 11 years after birth among boys and girls who later developed coronary heart disease. The mean z-scores for all boys and girls are set at zero. BMI, body mass index. Figure 1b shows the growth of the girls who later developed coronary heart disease. Similarly to the boys, their body size at birth was below the average. Their z-scores for BMI fell progressively in the first 6 months after birth and remained low at 2 years of age. After 4 years, they began to increase and continued to do so. In Table 1, findings for boys and girls have been combined to show the effect of low birthweight and low BMI at 2 years, divided into thirds, on coronary heart disease. The highest hazard ratios are among people with birthweights below 3.0 kg and BMIs at 2 years below 17 kg m−2. Table 2 shows the effects of BMI at 2 years and 11 years. BMI at each age is divided into thirds. The highest hazard ratios are among people whose BMI at 2 years was below 16 kg m−2, and whose BMI at 11 years was above 17.5 kg m−2. The results in Tables 1 and 2 were little changed by adjusting for adult social class and income. They show that the disease is associated with prenatal, infant and child growth. Rapid increase in z-score for BMI after 2 years of age predicted later coronary heart disease more strongly than a high BMI at any particular age. A sample of 2003 people in the Helsinki cohort, selected at random, have been examined (9). These findings show that small body size at birth, low BMI at 2 years and increase in BMI between 2 and 11 years are linked to the development of insulin resistance, a known risk factor for coronary heart disease and type 2 diabetes. This is consistent with findings in a longitudinal study of 1492 young men and women born in Delhi, India (15). In that study, thinness at around 2 years of age followed by rapid increase in BMI was associated with the development of type 2 diabetes at around the age of 30 years. Early growth may change the sensitivity of tissues to insulin by altering the composition of the body. Babies that have low birthweight and low weight gain during infancy lack muscle, a deficiency that will persist, as there is little cell division in muscle after infancy (16). If they gain weight rapidly in childhood, they may have a high fat mass in relation to muscle mass, which is known to be associated with insulin resistance (17). In the Helsinki studies, the path of growth that led to type 2 diabetes was similar to that which led to coronary heart disease. Slow growth in foetal life and infancy were followed by rapid increase in BMI after the age of 2 years (18). In contrast to children who later developed coronary heart disease, however, those who developed type 2 diabetes already had above-average BMI by the age of 5 years and their BMIs continue to rise thereafter. Underlying this rapid increase in BMI was an early ‘adiposity rebound’. Between birth and 1 year, babies acquire more muscle and fat and their BMI increases. After that age, as they grow taller they become slimmer. Around 6 years of age, they begin to get fatter again. This is known as the ‘adiposity rebound’ (19). The timing of the rebound, defined by the age at which the BMI is the lowest, is important. Children in whom it occurs early, at 4 or 5 years of age, have much higher rates of obesity in later life than children in whom it occurs at 7 or 8 years (20). The Helsinki studies show that early adiposity rebound also predicts type 2 diabetes in later life. The incidence of this disorder fell from 9% in people whose adiposity rebound occurred at 4 years of age or less to 2% in those in whom it occurred at 8 years or later (18). The age at adiposity rebound is strongly related to body size at 1 year. The Helsinki children who had low weight gain between birth and 1 year, and who were thin at 1 year, rebounded at an earlier age. It was not the overweight infant who was at risk of later type 2 diabetes but the underweight infant. Research around the world has shown that undernutrition and stunting of growth in early life promote adult obesity (21), although the processes are not understood. There is experimental evidence of a similar phenomenon in rodents and non-human primates 22-24). A relationship between childhood overweight and maternal overweight has been shown in many countries, although it remains unclear to what extent it reflects shared eating habits, prenatal effects on hormonal or metabolic settings, or some other process. High body mass increases the risk of gestational diabetes in the mother and type 2 diabetes in the offspring (25, 26). These offspring are born with excess fat and a high birthweight and they are obese during childhood. This is perhaps the clearest example of a link between events in utero and obesity in later life. Early observations on prenatal effects on obesity came from a study of young men born at the time of the Dutch famine of 1944–1945. Those who were conceived during the famine tended to be overweight (27). It is difficult, however, to generalize from this observation because the nutritional experience of these men was exceptional. Having been conceived during famine, food became abundant during the second half of their gestation. Studies in Europe and China have shown that people whose mothers had a low BMI during pregnancy tend to be insulin resistant and are therefore at increased risk of type 2 diabetes 28-30). This association extends across the normal range of mothers’ BMIs. Among men and women in Helsinki, plasma insulin concentration after a standard challenge with glucose fell progressively from 577 pmol L−1 in those whose mother had a BMI of 24 kg m−2 or less in late pregnancy to 405 pmol L−1 in those whose mother had a BMI of 29 kg m−2 or more (29). As BMI increases by around 3 kg m−2 during pregnancy, these findings indicate that foetuses make lifelong changes in their metabolism in responses to differences in their mothers’ BMIs within a range now regarded as optimal. The particular aspect of maternal metabolism that is linked to low BMI and causes insulin resistance in the offspring is not known. Low rates of release (turnover) of protein stored in muscle is one possibility (31). The limitations of BMI are well known. It does not distinguish fatness from muscularity, and takes no account of the site on the body where fat is deposited. Central adiposity, specifically high visceral fat, is associated with insulin resistance (32). People who had low birthweight tend to have central (upper body) adiposity. The extent of this tendency is being revealed now that Dexa scanning is replacing conventional measures of central adiposity such as waist circumference. One component of the tendency could be deposition of fat in the liver. There is a strong relation between liver fat content and insulin resistance (33). People from the Indian subcontinent tend to have a high fat mass in relation to their muscle mass, and high visceral fat mass. Their BMI, which tends to be low by European standards, does not describe this. Despite its limitations, BMI remains a practical way of monitoring childhood weight gain. One group of children that represents a major cause for concern is an invisible group, neither fat nor thin. They were thin at 2 years but are increasing their BMIs rapidly. To identify them will require serial measurement of BMI throughout childhood. The National Institute of Health in Washington recently concluded that coronary heart disease; hypertension, type 2 diabetes and obesity have their roots in prenatal and early prenatal life: ‘For example, coronary heart disease, the number one cause of death among adult men and women is more closely related to low birthweight than to known behavioural risk factors’ (34). Prevention of obesity-related disease may depend critically on improving the diet before the age of 2 years, although supervision through childhood will also be required. There is a widespread misunderstanding that undernutrition during infancy results from food insecurity. But many infants in homes where food is plentiful are underweight or stunted because of inappropriate feeding, inadequate care or recurrent minor illness. Infants use around 25% of their energy intake to sustain their rapid growth. After 2 years, growth slows and requires only 5% of energy. Infant growth is therefore especially vulnerable to undernutrition. If an infant becomes thin, it tries to compensate during childhood by rapid weight gain. The World Bank and other international agencies are increasingly aware that the adverse effects of poor growth between conception and 2 years of age – effects on health, brain development, educability and productivity – are largely irreversible. They advocate that this should be the focus for public health nutrition. There is an urgency about this. A quarter of all babies born in Britain today are recognizably thin, and the growth of many infants is suboptimal. There are large gaps in our knowledge of how to improve the nutrition of mothers and infants. The Southampton Women’s Survey, run by the University of Southampton, is the only large study in which women are recruited before pregnancy and the growth of their babies is measured in the womb, during infancy and into childhood. The nutrition of mothers, babies, infants and children is recorded in detail. This study provides a framework within which gaps in our knowledge can be addressed. A century ago, after the report of the interdepartmental committee, the British Government adopted a package of measures to improve the physique and the health of children. They were spectacularly successful. Children grew taller, became healthier and fewer of them died. There was, however, a cost. The age of puberty fell. People had longer lives but shorter childhoods. In retrospect, this was predictable: across the animal world, rapid growth is linked to early onset of reproduction. There seems no reason why action to reduce childhood obesity should not be effective. Within less than a century, public health legislation, increased availability of food and reduced physical activity has changed the body composition of British children. In recent years, cattle breeders have successfully improved the body composition of their stock, increasing muscle and reducing fat. So why would we be unable to do the same in our children? One explanation for the disappointing results of randomised trials to reduce obesity among school children is that they began too late. Growth and body composition may be easier to manipulate during infancy, and appetite and eating patterns become established at weaning. A long-term goal is improvement of foetal growth. Because a woman’s ability to nourish her offspring in the womb is established during her own foetal life, it will require at least one generation to optimize foetal nutrition. The expectation is, however, that improved body composition among young girls, with less fat but more height and skeletal mass, will lead to less fat and more muscular babies in the next generation. Trends in the body composition of newborn babies need to be monitored, in case there are unexpected costs of changing the body composition of young women. We have discovered the links between early growth and later disease because, in the past, birth size and infant and child growth were monitored and recorded. We need to resume this. No conflict of interest was declared.